Wildtype Neisseria meningitidis elaborate lipopolysaccharides without long O polysaccharide side chains, and are referred to as lipooligosaccharides (LOS). Others have shown that antibodies to meningococcal LOS determinants can be bactericidal. Studies have also shown that changes in the molecular size of the LOS in Haemophilus influenzae type b result in changes from serum resistance to serum sensitivity. Naturally occurring antibodies to the saccharide determinants of meningococcal LOS are present in the sera of healthy adults. Using changes in colony opacity and SDS-PAGE with silver staining, we selected a series of LOS variants from group B (BB-1 and 44/76) and group C (BB-305) N. meningitidis strains. No discernible difference were seen in the outer membrane proteins. We obtained sera from 4 healthy adults that had not worked with Neisseria. These sera were quickly frozen at -70 C to preserve complement activity. The sera were tested for bactericidal activity against each LOS variant by measuring Log decrease in viable count during 1 hour at 37 C. We found the BB-305 wildtype to be serum resistant (SR) in all 4 sera, but variant 1 (VI) was serum sensitive (SS) in all 4 sera. V2 was SR in 2 of 4 sera and SS in the other 2 sera. BB-305 wildtype LOS was 4800 daltons, V1 was 4300 daltons, and V2 was 3600 daltons. Loss of about two sugars from the wildtype resulted in a change from SR to SS, possible due to exposure of to a cross- reactive epitope. We are now using rabbit anti-LOS typing sera and monoclonals to determine epitope differences which may account for the differences in serum sensitivity.